FLEX Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 1294, Ready-to-Use (Dako Omnis), is intended for use in immunohistochemistry with the En Vision FLEX visualization system together with the Dako Omnis instrument to qualitatively detect human progesterone receptor in formalin-fixed, paraffin-embedded tissue sections of human breast cancer. The antibody binds progesterone receptor-expressing cells and is useful in the assessment of progesterone receptor status in human breast carcinomas.

The clinical interpretation of any staining or its absence should be complemented by morphological studies using proper controls and should be evaluated within the context of the patient's clinical history and other diagnostic tests by a qualified pathologist. This antibody is intended to be used after the primary diagnosis of tumor has been made by conventional histopathology using nonimmunologic histochemical stains.

Device Description

FLEX Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 1294, Readyto-Use (Dako Omnis) is utilized to perform a qualitative immunohistochemical (IHC) assay to identify progesterone receptor (PR) expression in formalin fixed human breast cancer tissues routinely processed and paraffin-embedded for histological examination. The proposed device is a variant of FLEX Monoclonal Mouse Anti-Human Progesterone Receptor intended for use with the automated slide staining instrument Dako Omnis.

The design of the proposed device is developed to provide equivalent performance to its predicate FLEX Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 636, Ready-to-Use, (Link) with adaptation of the product configuration, to be used on the Dako Omnis Instrument instead of the Autostainer Link 48 Instrument.

The antibody is provided in liquid form in a buffer containing stabilizing protein and 0.015 mol/L sodium azide. The proposed device is intended for automated immunohistochemical (IHC) slide staining with the Dako Omnis Instrument and the software performing and controlling the automated slide staining process is validated for its intended use.

AI/ML Overview

The provided text is a 510(k) summary for the FLEX Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 1294, Ready-to-Use (Dako Omnis). This document focuses on demonstrating substantial equivalence to a predicate device rather than presenting a detailed clinical study with acceptance criteria for a new AI/software device. Therefore, a direct response to some of the requested points (e.g., human reader improvement with AI, standalone performance, specific ground truth methods with expert numbers) is not fully achievable from this document.

However, I can extract information related to the device's performance evaluation and its acceptance criteria as presented for regulatory approval.

Acceptance Criteria and Reported Device Performance

The document states that "All results from performance studies confirm that the device meets its acceptance criteria and is substantial equivalent to its predicate device." While specific numerical acceptance criteria are not explicitly tabulated, the performance characteristics evaluated were focused on:

Analytical specificity for normal tissue: This implies the device should not show staining in normal tissues that do not express progesterone receptor, thus minimizing false positives.
Reproducibility: This measures the consistency of results within a run, between different lots of reagents, across different laboratories, and among different observers.
Concordance with the predicate device: This is a key acceptance criterion for substantial equivalence, aiming to show that the new device produces results that agree sufficiently with an already approved device.

Since the document concludes that the device meets its acceptance criteria, the reported device performance is implicitly that these aspects were successfully demonstrated.

Acceptance Criteria Category	Reported Device Performance
Analytical Specificity	Device demonstrates analytical specificity for normal tissue (e.g., minimal false positives in non-PR expressing normal tissues). The exact metric (e.g., % specificity) is not provided.
Reproducibility	Device demonstrates acceptable intra-run, inter-lot, inter-laboratory, and inter-observer reproducibility. The exact metrics (e.g., % agreement, kappa scores) are not provided.
Concordance	Device demonstrates substantial equivalence (sufficient agreement) with the predicate device (FLEX Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 636, Ready-to-Use, (Link)). The exact concordance metrics are not provided.

Study Details from the Document:

Sample size used for the test set and the data provenance: The document mentions a "concordance study" but does not specify the sample size for the test set (number of cases or tissue sections) or the data provenance (e.g., country of origin, retrospective/prospective).
Number of experts used to establish the ground truth for the test set and the qualifications of those experts: The document states that "The clinical interpretation of any staining or its absence... should be evaluated within the context of the patient's clinical history and other diagnostic tests by a qualified pathologist." This indicates that pathologists are involved in interpretation but does not specify the number or specific qualifications (e.g., years of experience) of experts used to establish the ground truth for the test set in the analytical or concordance studies mentioned.
Adjudication method (e.g. 2+1, 3+1, none) for the test set: Not specified in the provided text.
If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance: This is not an AI/software device. It is an immunohistochemistry (IHC) reagent used with an automated staining instrument. Therefore, an MRMC study comparing human readers with and without AI assistance is not applicable and was not performed. The study evaluates the performance of the IHC reagent itself.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done: This question is not directly applicable as the device is an IHC reagent and an automated staining platform, not an AI algorithm. The performance evaluation is inherently "standalone" in terms of the reagent's analytical performance, but its interpretation requires a "human-in-the-loop" (a pathologist).
The type of ground truth used (expert consensus, pathology, outcomes data, etc.): The ground truth for this type of device, aimed at detecting progesterone receptor expression, is typically established by pathological assessment of the stained tissue sections, often comparing the new device's staining patterns and intensity against a gold standard or the predicate device's results. The interpretation is done by "qualified pathologists."
The sample size for the training set: The document does not describe a "training set" in the context of machine learning. For an IHC reagent, "training" would refer to internal development and optimization, not a distinct dataset for algorithm training.
How the ground truth for the training set was established: As above, the concept of a "training set" and its ground truth in the AI/ML sense is not applicable to this device. Quality control and optimization during the development of the reagent and staining protocol would rely on expert pathological evaluation.

Summary

{0}------------------------------------------------

Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

December 21, 2017

Dako Denmark A/S Lasse Post Møller Pathology Regulatory Affairs Manager Produktionsvej 42 DK-2600 Glostrup, Denmark

Re: K170005

Trade/Device Name: FLEX Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 1294, Ready-to-Use (Dako Omnis) Regulation Number: 21 CFR 864.1860 Regulation Name: Immunohistochemistry reagents and kits Regulatory Class: Class II Product Code: MXZ Dated: December 28, 2017 Received: January 3, 2017

Dear Lasse Post Møller:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR

{1}------------------------------------------------

Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Reena Philip -S

Reena Philip, Ph.D. Director Division of Molecular Genetics and Pathology Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

{2}------------------------------------------------

Indications for Use

510(k) Number (if known) K170005

Device Name

FLEX Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 1294, Ready-to-Use (Dako Omnis)

Indications for Use (Describe)

For in vitro diagnostic use.

Type of Use (Select one or both, as applicable)
-------------------------------------------------

X Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

{3}------------------------------------------------

5. 510(k) Summary

Traditional Premarket Notification Submission (510(k)) Summary Prepared in accordance with 21 CFR 807.92

Submitter Information

Dako Denmark A/S

Produktionsvej 42

2600 Glostrup, Denmark

Establishment registration No: 9610099

Contact Information

Lasse Post Møller Dako Denmark A/S Produktionsvej 42 2600 Glostrup, Denmark Telephone: +45 5167 6362 Telefax: +45 8830 5998 Email: lasse.moller@agilent.com

Date Summary Prepared

December 21, 2017

Device Name(s)

Trade name(s)	FLEX Monoclonal Mouse Anti-Human ProgesteroneReceptor, Clone PgR 1294, Ready-to-Use (DakoOmnis)
Product code:	GA090
Common name	Anti-Human PR, Clone PgR 1294 (Dako Omnis)
Classification:	Class II (21 CFR 864.1860)
FDA Product Code:	MXZ

{4}------------------------------------------------

Predicate Device:

Trade name(s):	FLEX Monoclonal Mouse Anti-HumanProgesterone Receptor, Clone PgR 636, Ready-to-Use, (Link)
Product code:	IR068
Classification:	Class II (21 CFR 864.1860) FDA Product Code: MXZ
Device cleared in Premarket notification K130861.

Device Description

Intended Use:

For in vitro diagnostic use.

{5}------------------------------------------------

FLEX Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 1294, Readyto-Use (Dako Omnis), is intended for use in immunohistochemistry with the EnVision FLEX visualization system together with the Dako Omnis instrument to qualitatively detect human progesterone receptor in formalin-fixed, paraffin-embedded tissue sections of human breast cancer. The antibody binds progesterone receptor-expressing cells and is useful in the assessment of progesterone receptor status in human breast carcinomas.

Substantial Equivalence

The proposed device, FLEX Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 1294, Ready-to-Use (Dako Omnis) is claimed to be substantially equivalent to the predicate FLEX Monoclonal Mouse Anti- Human Progesterone Receptor, Clone PgR 636, Ready-to-Use, (Link). The predicate device IR068 is cleared for the US market in the premarket notification K130861.

Both products have the same intended use and specifically bind to progesterone receptor (PR) proteins located in the nuclei of cells. Both products require similar detection chemistry principles for visualization of antigens, and both aid in the prognosis of breast carcinoma.

All differences between the proposed device and its predicate are related to their use with different slide staining instruments, see details in the comparison table below.

Similarities
Item	Device	Predicate
Intended Use	Detection of progesteronereceptor	Same
Antibody Type	Monoclonal, mouse origin	Same

{6}------------------------------------------------

Isotype	IgG	Same
Staining Pattern	Nuclear	Same
Positive Cell Type	Cells expressingprogesterone	Same
Interpretation of results	Positive: ≥1% positivestaining breast cancer cells	Same
Tissue Type	Formalin-fixed paraffin-embedded breast cancer	Same
Technology	Immunohistochemistry	Same
Storage	2-8 °C	Same

Differences
Item	Device	Predicate
Clone	Clone PgR 1294	Clone PgR 636
Configuration	Pre-diluted-Ready-to-usewith Dako Omnis	Pre-diluted-Ready-to-use withAutostainer Link 48
TemperatureControl/IncubationTemperature	Temperature controlled at$32°C ± 2°C$	No temperaturecontrol (ambienttemperature)
Antibody IncubationTime*	10 minutes	20 minutes
Onboard Stability	80 hours	Not defined norapplicable
Staining	Dynamic gap staining:Reagent is applied anddistributed across slide viaactive slide lids whichenable capillary forcespreading	Open slide staining:Reagent is appliedand distributedacross slide viagravitationalspreading
Vial	Dako Omnis Large Vial, 30mL	Automation Vial,25mL
Cap	Dako Omnis Closureincluding septum	White Nalgene Cap
Deparaffinization	Onboard Dako Omnis withClearify	Envision FLEXHigh pH on externalPT Module
Pre-Treatment (AntigenRetrieval)	EnVision FLEX High pH(30 minute heat-inducedepitope retrieval)	EnVision FLEXHigh pH (20 minuteheat-induced epitoperetrieval)
Visualization	EnVision FLEX(Chromogen 5 minutes)	EnVision FLEX(Chromogen 2x5minutes)

{7}------------------------------------------------

Performance Characteristics

Performance characteristics of the device were evaluated to determine its analytical specificity for normal tissue and reproducibility to control intra-run, inter-lot, inter-laboratory and inter-observer variations. The device was also evaluated in a concordance study to establish equivalence to the predicate device. All results from performance studies confirm that the device meets its acceptance criteria and is substantial equivalent to its predicate device.

Therefore, based on the information provided in this premarket notification, Dako concludes that the FLEX Monoclonal Mouse Anti-Human Progesterone Receptor, Clone PgR 1294, Ready-to-Use (Dako Omnis) is safe, effective and substantially equivalent to the predicate device in the indication for use, device design, materials, operational principles, and intended use.

Regulation Number and Section

§ 864.1860 Immunohistochemistry reagents and kits.

(a)
Identification. Immunohistochemistry test systems (IHC's) are in vitro diagnostic devices consisting of polyclonal or monoclonal antibodies labeled with directions for use and performance claims, which may be packaged with ancillary reagents in kits. Their intended use is to identify, by immunological techniques, antigens in tissues or cytologic specimens. Similar devices intended for use with flow cytometry devices are not considered IHC's.(b)
Classification of immunohistochemistry devices. (1) Class I (general controls). Except as described in paragraphs (b)(2) and (b)(3) of this section, these devices are exempt from the premarket notification requirements in part 807, subpart E of this chapter. This exemption applies to IHC's that provide the pathologist with adjunctive diagnostic information that may be incorporated into the pathologist's report, but that is not ordinarily reported to the clinician as an independent finding. These IHC's are used after the primary diagnosis of tumor (neoplasm) has been made by conventional histopathology using nonimmunologic histochemical stains, such as hematoxylin and eosin. Examples of class I IHC's are differentiation markers that are used as adjunctive tests to subclassify tumors, such as keratin.(2) Class II (special control, guidance document: “FDA Guidance for Submission of Immunohistochemistry Applications to the FDA,” Center for Devices and Radiologic Health, 1998). These IHC's are intended for the detection and/or measurement of certain target analytes in order to provide prognostic or predictive data that are not directly confirmed by routine histopathologic internal and external control specimens. These IHC's provide the pathologist with information that is ordinarily reported as independent diagnostic information to the ordering clinician, and the claims associated with these data are widely accepted and supported by valid scientific evidence. Examples of class II IHC's are those intended for semiquantitative measurement of an analyte, such as hormone receptors in breast cancer.
(3) Class III (premarket approval). IHC's intended for any use not described in paragraphs (b)(1) or (b)(2) of this section.
(c)
Date of PMA or notice of completion of a PDP is required. As of May 28, 1976, an approval under section 515 of the Federal Food, Drug, and Cosmetic Act is required for any device described in paragraph (b)(3) of this section before this device may be commercially distributed. See § 864.3.